Project Summary: The objective of the proposed work is to develop a novel molecular imaging technique, photothermal optical coherence tomography (photothermal OCT), and use this technology along with existing OCT technologies (Doppler OCT) to monitor cancer therapy. Combined photothermal and Doppler OCT would be a powerful tool to monitor the vascular response to anti-angiogenic drugs, due to its high resolution, chemical specificity, flow imaging capabilities and relatively high penetration depths. The first aim of this work is to develop and validate a photothermal OCT system with laser-heated gold nanoshells as the photothermal source in tissue-like phantoms. The photothermal OCT system will include a pre-existing Doppler OCT system and an amplitude-modulated near infrared (NIR) heating laser. Phantoms containing gold nanoshells that absorb in the NIR (the optical window where light penetrates deepest in tissue), polystyrene spheres as scatterers and hemoglobin as an absorber will be used to characterize the photothermal signal from gold nanoshells in a tissue-like environment. The second aim is to test the potential for Doppler OCT to measure changes in tumor microvascular flow rates in response to anti- angiogenic drugs in vivo in an animal model. Vascular endothelial growth factor (VEGF) is an angiogenic factor that is overexpressed in certain types of cancers. Bevacizumab is an anti-human VEGF antibody that induces tumor shrinkage in patients with solid tumors. Real time Doppler OCT (an existing technology) will be used to image flow rates in the microvessels of colon cancer tumors grown in dorsal skin flap mouse window chamber model before and at specific time points after bevacizumab treatment, and in control animals without bevacizumab treatment. The third and final aim of the proposed work is to test the potential for combined photothermal and Doppler OCT imaging of tumor microvascular VEGF levels and flow rates in response to anti-angiogenic drugs in vivo. Gold nanoshells, bioconjugated to antibodies against the VEGF receptor, will be intraveneously injected into the tumor vasculature of the mice. Photothermal and Doppler OCT will be used to image the amount and distribution of VEGF receptors, and microvessel flow rates, respectively, in control animals and in bevacizumab-treated animals before and at distinct time points after bevacizumab treatment. Relevance: The majority of cancer deaths are due to metastatic disease that fails to respond to chemotherapeutic drugs. This work could provide a minimally invasive method to monitor and study tumor response to cancer therapy in animal models. In the future, this technology could be used to provide individualized care to cancer patients, thus decreasing cancer morbidity and mortality.